Indications
Lansoprazole is primarily indicated for reducing gastric acid secretion. It is approved for the short-term treatment of several gastrointestinal conditions, such as active gastric ulcers, active duodenal ulcers, erosive reflux esophagitis, symptomatic gastroesophageal reflux disease (GERD), and ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) in both gastric and duodenal contexts. Additionally, lansoprazole can be utilized for the maintenance and healing of conditions like duodenal ulcers, NSAID-related gastric ulcers, and erosive esophagitis. It is effective in preventing the recurrence of gastric ulcers in patients with a history of such conditions who also require chronic NSAID therapy. Lansoprazole is also beneficial in managing hypersecretory conditions, including Zollinger-Ellison syndrome, and is effective in eradicating Helicobacter pylori when used in combination with antibiotics such as amoxicillin and clarithromycin (triple therapy) or with amoxicillin alone (dual therapy).
Pharmacodynamics
Lansoprazole functions by decreasing gastric acid secretion through its action on the H+,K+-ATPase enzyme, which catalyzes the final step in acid secretion within parietal cells. This mechanism allows lansoprazole to effectively inhibit both daytime and nocturnal acid secretion, irrespective of the time of administration. Lansoprazole is thus effective in healing duodenal ulcers, reducing ulcer-associated pain, and alleviating heartburn symptoms. Furthermore, it decreases pepsin secretion, making it a suitable treatment for hypersecretory conditions like Zollinger-Ellison syndrome.
Absorption
The oral bioavailability of lansoprazole ranges between 80% to 90%, with peak plasma concentration (Cmax) typically achieved approximately 1.7 hours post oral administration. It is important to note that food intake significantly reduces the absorption of lansoprazole, as evidenced by a 50% to 70% reduction in both Cmax and area under the curve (AUC). For this reason, patients are advised to take lansoprazole prior to meals to ensure optimal absorption.
Metabolism
Lansoprazole undergoes predominant metabolism in the liver, primarily facilitated by the cytochrome P450 enzymes CYP3A4 and CYP2C19. The major metabolites resulting from this metabolic pathway are 5-hydroxy lansoprazole and the sulfone derivative of lansoprazole. Understanding these metabolic processes is crucial for anticipating potential drug interactions and variations in drug response among individuals with different CYP2C19 genotypes.
Mechanism of Action
Lansoprazole functions as a proton pump inhibitor (PPI) and acts as a prodrug, necessitating activation within an acidic environment through protonation. Upon activation, lansoprazole targets and reacts with cysteine residues, specifically Cys813 and Cys321, on the gastric enzyme H+,K+-ATPase located in parietal cells. This interaction results in the formation of stable disulfide bonds, effectively inhibiting the enzyme's activity. Such covalent binding contributes to the prolonged suppression of gastric acid secretion, a characteristic feature of proton pump inhibitors.
